Calculating Maximum Allowable Carryover (MAC) in Cleaning Validation

Hello everyone. In this article, we will discuss how to calculate the Maximum Allowable Carryover (MAC), which plays a critical role in cleaning validation in the pharmaceutical industry.

Role and Structure of Cleaning Validation

The cleaning validation process is essential to ensure the safety and quality of pharmaceutical products. Each cleaning validation process is unique, influenced by factors such as raw materials, process flow diagrams, operating procedures, and the minimum batch size.

The process consists of three stages: design, qualification, and verification. These stages must be continuously reviewed and updated throughout the lifecycle of the process.

Definition and Necessity of MAC

When switching between products, it is necessary to determine the amount of the previous product that may remain without posing a risk to patients in the next product. This amount is known as the Maximum Allowable Carryover (MAC).

Methods for Calculating MAC

There are two main approaches to calculating MAC:

• Using TDD (Total Daily Dose): This method calculates MAC based on the current and next product information, using a safety factor (typically 1000) derived from a risk assessment.
• Using LD₅₀ (Median Lethal Dose): This method calculates the No-Observed-Effect Level (NOEL) from the LD₅₀ of Product A and then derives the MAC.

Deriving Product Limits and TOC Limits from MAC

Once the MAC is determined, the next step is to calculate the product-specific limit. Common sampling methods include:

• Swab samples
• Rinse samples

Additionally, the TOC (Total Organic Carbon) limit can be calculated by multiplying the product-specific limit by the compound’s carbon content percentage.

FDA Guidance and Lifecycle Approach

Recent FDA guidance recommends a lifecycle approach to cleaning validation, where non-specific analytical methods such as TOC are considered best practice. This allows for more flexible and practical validation processes.

Conclusion

Accurate calculation of MAC is crucial for ensuring product safety and quality in cleaning validation. A well-structured process based on quantitative and scientifically justified assessments is essential.

We hope this information proves useful to your work.

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